Escherichia coli infection induces only fetal thymus-derived γδ T cells at the infected site

Abstract

Intraperitoneal infection of mice with Escherichia coli induced activated TCR γδ T cells in the peritoneal cavity. We provide evidence that the E. coli-induced γδ T cells are derived only from the fetal thymus on the following grounds. The γδ T cells were not induced in athymic nude mice and irradiated bone marrow-transferred mice which lack fetal thymus-derived T cells. However, E. coli infection of fetal thymus-grafted nude mice did induce fetal thymus-derived γδ T cells. These results suggest that the fetal thymus-derived γδ T cells colonize the periphery during early ontogeny, and are maintained until adult age. The E. coli-induced γδ T cells express only the Vδ1 gene. Vγ6 was predominantly expressed whereas anti-Vγ1 and anti-Vγ4 monoclonal antibodies stained less than 3% of the cells. Direct sequencing of PCR products revealed that Vγ6 and Vδ1 genes expressed by the E. coli-induced γδ T cells were invariant sequences identical to those expressed in the fetal thymus. The antigen (Ag) specificity of a T cell hybridoma expressing the fetal type Vγ6/Vδ1+ TCR could not be identified as the cells failed to respond to lipopolysaccharide, E. coli Ag, mycobacterial heat shock protein 65, or isopentenyl pyrophosphate. These results suggest that the Vγ6/Vδ1+ γδ T cells derived from fetal thymus can participate in immune responses against bacterial infection through recognition of a novel class of Ag which is not yet identified.